|Year : 2019 | Volume
| Issue : 3 | Page : 180-186
Adaptive radiotherapy in non-small cell lung cancers: Is there a dosimetric benefit of volumetric modulated arc radiotherapy over three-dimensional conformal radiotherapy?
Anshuma Bansal, Rajit Rattan, Rakesh Kapoor, Reena Kumari
Department of Radiotherapy, PGIMER, Chandigarh, India
|Date of Submission||15-Mar-2019|
|Date of Acceptance||24-Jun-2019|
|Date of Web Publication||05-Aug-2019|
Dr. Anshuma Bansal
Department of Radiotherapy, PGIMER, Chandigarh
Source of Support: None, Conflict of Interest: None
AIM: The study aimed to evaluate the change in gross tumor volume (GTV) in pretreatment and mid-treatment planning computed tomography (CT) scans, to find its dosimetric impact on normal tissue sparing when doing adaptive radiotherapy in lung cancers, and to do dosimetric comparison between volumetric modulated arc radiotherapy (VMAT) and three-dimensional conformal radiotherapy (3DCRT) plans.
MATERIALS AND METHODS: Fifteen patients with advanced non-small cell lung cancer, planned for radical radiotherapy, underwent planning CT scans at baseline and after 40 Gy. Target volumes were delineated on both scans, and both 3DCRT and VMAT plans were made. Phase I delivered 40 Gy to initial planning target volume (PTV). Two Phase II plans for 20 Gy to PTV boost were developed on initial and mid-treatment scans. Plan sums were made. Volumetric and dosimetric changes in target volumes and normal structures were analyzed.
RESULTS: There was a significant reduction in primary GTV (31.26%; P = 0.001) and PTV (28.07%; P = 0.001) in mid-treatment CT scan. VMAT plans were superior to 3DCRT plans in terms of lesser V20 and V5 doses to the ipsilateral lung (V20: 33.03% vs. 58.89%; P = 0.00 and V5: 63.62% vs. 77.20%; P = 0.001), lesser V5 doses to the contralateral lung (V5: 19.12% vs. 32.16%; P = 0.03), and lesser mean doses to the heart (12.61 Gy vs. 15.06 Gy; P = 0.02); however, PTV coverage was similar in both the plans. Among the two Phase II VMAT plans, those made on mid-treatment CT scans were superior in terms of V5 doses to the contralateral lung (5.23% vs. 7.99%; P = 0.001), mean dose to bilateral combined lung (3.57 Gy vs. 5.10 Gy; P = 0.03), and Dmax spinal cord (7.90 Gy vs. 11.36 Gy; P = 0.05).
CONCLUSION: The study demonstrates the superiority of VMAT plans over 3DCRT plans and emphasizes the need for adaptive radiotherapy planning with VMAT in lung cancers for minimizing normal tissue toxicity without compromising local control.
Keywords: Adaptive radiotherapy, lung cancer, three-dimensional conformal radiotherapy, volumetric modulated arc radiotherapy
|How to cite this article:|
Bansal A, Rattan R, Kapoor R, Kumari R. Adaptive radiotherapy in non-small cell lung cancers: Is there a dosimetric benefit of volumetric modulated arc radiotherapy over three-dimensional conformal radiotherapy?. Int J Health Allied Sci 2019;8:180-6
|How to cite this URL:|
Bansal A, Rattan R, Kapoor R, Kumari R. Adaptive radiotherapy in non-small cell lung cancers: Is there a dosimetric benefit of volumetric modulated arc radiotherapy over three-dimensional conformal radiotherapy?. Int J Health Allied Sci [serial online] 2019 [cited 2019 Aug 20];8:180-6. Available from: http://www.ijhas.in/text.asp?2019/8/3/180/263940
| Introduction|| |
Lung cancer is the most common cause of cancer-related death worldwide. New cases account for 12% of all annually diagnosed cancer cases. Chemoradiation is the standard of care for advanced stage and inoperable patients; still, the prognosis is poor due to locoregional failure or distant metastases. Multiple dose-escalation trials have reported better local control with decreased relapse rates and increased survival., However, RTOG 0617 has shown negative results in terms of higher locoregional failures and shorter overall survival with dose escalation and may be caused by detrimental effects from high-dose three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (IMRT) on normal lungs and heart. Auperin et al. in their meta-analysis concluded that improved local control rates influence overall survival. However, the major limiting factor in dose escalation is the tolerance of normal tissues, such as the lung, heart, and spinal cord., Radiation pneumonitis is one of the major dose-limiting toxicities in lung cancer. Nowadays, its occurrence and severity correlate well with V20 and mean lung dose.,
Modern radiotherapy techniques, such as IMRT and volumetric modulated arc radiotherapy (VMAT), can potentially improve target coverage with a much steeper dose gradient and minimize irradiated normal tissue volumes.,, However, there are certain uncertainties in the image-guided radiotherapy planning. One such uncertainty is tumor volume shrinkage which is a well-known fact during the treatment for lung cancer., It is estimated that daily tumor shrinkage varies between 0.6% and 2.4%.,,, In the current study, we aimed to estimate the dosimetric benefit of planning by VMAT compared to 3DCRT when patients are treated by adaptive radiotherapy. Furthermore, we will quantify the degree of tumor volume change during the course of radiotherapy and its impact on normal tissue sparing.
| Materials and Methods|| |
This is a prospective study conducted in 15 patients of biopsy-proven non-small cell carcinoma lung, with Karnofsky Performance Status ≥80, after informed consent. All patients were treated by standard chemoradiation protocol followed in our department. Patients with age <18 years, pregnant, having prior malignancy of any other site, and postoperative or Stage IV disease were excluded from the study. All patients underwent standard clinical staging workup which included complete medical history and a systemic physical examination, contrast-enhanced computed tomography (CECT) of the chest, abdomen, and pelvis/positron-emission tomography (positron-emission tomography–CT scan), and CT-guided fine-needle aspiration cytology/endobronchial biopsy from the growth.
All patients underwent planning four-dimensional (4D) CECT scan prior to treatment and a repeat scan after 40 Gy for boost phase. The gross tumor volume (GTV) was delineated on the maximum intensity projection (MIP) images of 4DCT scan. Lymph nodes were defined to be involved if their short axis is 10 mm on CT. GTV-P was a gross primary disease, and GTV-N was a gross nodal disease as seen on imaging. The clinical target volume (CTV) for both gross primary tumor and gross nodes was generated by adding a 6–8 mm margin to the respective GTV in all dimensions, depending on the histology (6 mm for squamous cell carcinoma and 8 mm for adenocarcinoma). Since GTV was delineated on MIP images, and CTV margin was given over GTV, therefore, the CTV itself accounted for internal target volume (ITV). The planning target volume (PTV) was generated with a 5 mm expansion of ITV as per the institutional protocol for setup uncertainties. No elective irradiation of the lymphatic regions was conducted.
After 40 Gy of radiation, repeat 4DCT was performed. The targets as well as normal tissue contours (ipsilateral lung) were modified on the second scan to adapt to tumor volume change. For GTV-N, the nodes considered significant on the baseline scan were identified and contoured, irrespective of the size criteria. Normal structures (ipsilateral lung, contralateral lung, heart, and spinal cord) were contoured.
Treatment planning was performed on treatment planning system. Both the 3DCRT plans and the VMAT plans were made, and the final dose distribution was calculated.
Three-dimensional conformal radiotherapy planning
The Phase I plan of 40 Gy delivered in 20 fractions (40 Gy/20#/4 weeks) was made using 2–3 photon fields using multileaf collimators. The Phase II plan of 20 Gy/10#/2 weeks was made mostly by 3 or 4 angled photon fields to spare normal structures as much as possible. All the plans were aimed to deliver the 95% isodose volume to the PTV.
Volumetric modulated arc radiotherapy planning
All initial and mid-treatment plans were aimed to deliver the 95% isodose volume to the PTV while respecting the dose constraints to the organs at risk. Specifically, for the combined plan, the tissue volume outside the PTV was constrained to receive the following doses: for lung: V20 <35% (volume of lung receiving 20 Gy should be <35%), for heart: V20 <20%, and the maximal spinal cord dose was limited to 45 Gy. The dose constraints for each phase were given separately to obtain the above-mentioned combined doses and are given below:
- Phase I (40 Gy/20#/2 weeks): Ipsilateral lung (outside PTV) V20 <20% and V15 <30%, contralateral lung V5 <20%, both lung mean dose <9 Gy, heart V15 <20%, and spinal cord maximum dose: 35 Gy
- Phase II (20 Gy/10#/2 weeks): Ipsilateral lung (outside PTV) V10 <20% and V5 <30%, contralateral lung V5 <10%, both lung mean dose <4 Gy, heart V5 <20%, and spinal cord maximum dose 10 Gy.
This Phase II plan was made on both pretreatment planning CT scan (plan A) and mid-treatment planning CT scan (plan B).
Patients were treated with the 3DCRT planning for both the phases.
Planning target volume coverage
Comparison was made between the PTV coverage among the two plans by VMAT and 3DCRT in terms of V95 and V100 (volume receiving 95% and 100% of the prescribed dose, respectively).
Comparisons were done for the doses received by the ipsilateral lung, contralateral lung, heart (V5, V20, and mean dose [Dmean]), and spinal cord (Dmax) by the 3DCRT and VMAT plans.
Dose variation in Phase II volumetric modulated arc radiotherapy plans between initial planning computed tomography (plan A) and mid-treatment planning computed tomography (plan B)
The reduction in doses to ipsilateral lung PTV, ipsilateral lung, contralateral lung and heart (V5, V20, and mean dose [Dmean]), and spinal cord (Dmax) was assessed between the VMAT Phase II plans made on initial planning CT and mid-treatment planning CT.
SPSS version 19.0 (Statistical Package for the Social Sciences Inc, Chicago, Illinois, USA, SPSS Inc.) software was used for statistical analysis. Target volumes (including GTV and PTV), before and after 40 Gy, were measured. The Wilcoxon signed-rank test was used to compare dosimetric parameters between the 3DCRT and VMAT plans and the two Phase II VMAT plans (plan A: made on initial CT and plan B: made on repeat CT). Independent t-test was used to compare the means and the volume reduction. The statistical difference was considered statistically significant at P < 0.05.
| Results|| |
The mean age of the patient cohort (12 males and 3 females) was 53.5 years (range, 39–65 years) [Table 1]. Of 15 patients, 6 patients had IIIA and 9 patients had IIIB disease. All 15 patients had node-positive disease and nine had right-sided primary tumors. Twelve patients received concurrent chemotherapy.
Dosimetric comparison of three-dimensional conformal radiotherapy and volumetric modulated arc radiotherapy plans
PTV coverage was adequately achieved by both the plans [Table 2]. VMAT plans, however, were dosimetrically superior to 3DCRT plans in terms of doses received by the ipsilateral lung (V20 and V5), contralateral lung (V5), and heart (V20 and mean dose). For ipsilateral lung, V20 was 33.03 ± 3.67% by VMAT plans versus 58.89 ± 6.69% by 3DCRT plans (P = 0.00) and V5 was 63.62 ± 7.20% by VMAT plans versus 77.20 ± 5.29% by 3DCRT plans (P = 0.01). V5 for contralateral lung was 13.05% less for VMAT plans compared to 3DCRT plans. V20 and mean heart dose were also significantly less for VMAT plans versus 3DCRT plans. [Figure 1] represents the dose-volume histograms (DVHs) comparing doses received by normal structures among VMAT and 3DCRT plans.
|Table 2: Dose variation between three-dimensional conformal radiotherapy and volumetric modulated arc radiotherapy plans|
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|Figure 1: Dose-volume histogram comparing the heart (pink), contralateral lung (green), bilateral lung (yellow), ipsilateral lung (blue), and spinal cord (r) among volumetric modulated arc radiotherapy and three-dimensional conformal radiotherapy plans|
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Volumetric change between initial and mid-treatment scans
Shrinkage in target volume was observed for all patients in the mid-treatment scan. The mean GTV-P, GTV-N, and PTV on the initial scans were 125.59 ± 104.32, 14.17 ± 22.15, and 262.96 ± 197.29 cm3, respectively [Table 3]. On mid-treatment scans, mean GTV-P reduced to 86.33 ± 68.64 cm3 (P = 0.001; median reduction, 31.26%), mean GTV-N reduced to 7.02 ± 10.95 cm3 (P = 0.02; median reduction, 50.0%), and mean PTV reduced to 189.13 ± 131.56 cm3 (P = 0.001; median reduction, 28.07%).
|Table 3: Tumor volume in initial planning computed tomography and mid-treatment planning computed tomography scans|
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Dosimetric changes in Phase II volumetric modulated arc radiotherapy plans between initial planning computed tomography (plan A) and mid-treatment planning computed tomography (plan B)
In comparison with plan A, in plan B, for the ipsilateral lung, V20 reduced to 2.10% from 5.25% (P = 0.06); however, V5 and mean ipsilateral lung dose could not show a statistically significant reduction [Table 4]. For the contralateral lung, V5 reduced by 2.76% (P = 0.001) in plan B, and for the combined lung, mean dose reduced by 30% (P = 0.03). On comparing dose-volume parameter for the heart, none of the plan B parameters showed a significant decrease compared to those of plan A. Spinal cord dose, however, showed 30% decrease from 11.36 ± 2.25 Gy in plan A to 7.90 ± 1.12 Gy in plan B. [Figure 2]a and [Figure 2]b represents the DVHs comparing doses received by normal structures and PTV boost among the VMAT boost plans made on the initial planning CT (plan A) and mid-planning CT scans (plan B) respectively.
|Table 4: Dose variation in Phase II volumetric modulated arc radiotherapy (VMAT) plans made on initial planning CT (plan A) and mid-treatment planning CT (plan B)|
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|Figure 2: (a) Dose-volume histogram showing doses received by the heart (pink), contralateral lung (green), bilateral lung (yellow), ipsilateral lung (blue), spinal cord (orange), and planning target volume boost by volumetric modulated arc radiotherapy plans, made on initial planning computed tomography scan (plan A). (b) Dose-volume histogram showing doses received by the heart (pink), contralateral lung (green), bilateral lung (yellow), ipsilateral lung (blue), spinal cord (orange), and planning target volume boost by volumetric modulated arc radiotherapy plans, made on mid planning computed tomography scan (plan B)|
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| Discussion|| |
3DCRT technique has long been used for radiotherapy treatment planning of patients with non-small cell lung cancer. The major limitation while planning patients with this technique is that dose escalation beyond certain limit is usually not possible without causing excess damage to normal tissues (lung, heart, and spinal cord), whereas in lung cancers, the benefit of higher doses in terms of better local control and overall survival has already been demonstrated by multiple studies.,, Another inevitable fact in lung cancers is tumor movement along with respiration, which makes treatment delivery with 3DCRT all the more difficult. In practice, the above two shortcomings can be dealt using inverse planning (IMRT or VMAT) and image guidance techniques, respectively. In our study also, we have tried to find whether there is any dosimetric advantage in terms of tumor volume coverage and doses to normal tissues by VMAT planning in comparison to 3DCRT planning.
In all our patients, PTV coverage was adequately achieved by both the plans. VMAT plans, however, were dosimetrically superior to 3DCRT plans in terms of doses received by the ipsilateral lung (V20 and V5), contralateral lung (V5), and heart (V20 and mean dose). For the ipsilateral lung, V20 was 33.03 ± 3.67% by VMAT plans versus 58.89 ± 6.69% by 3DCRT plans (P = 0.00) and V5 was 63.62 ± 7.20% by VMAT plans versus 77.20 ± 5.29% by 3DCRT plans (P = 0.01). V5 for the contralateral lung was 13.05% less for VMAT plans compared to 3DCRT plans. V20 and mean heart dose were also significantly less for VMAT plans versus 3DCRT plans.
Similar results were demonstrated by Elwan et al. who found that VMAT plans displayed lower mean lung dose (P < 0.001), V20 (P < 0.001), and mean dose to the heart (P = 0.006) compared to 3DCRT plans. 3DCRT plans, however, delivered a lower maximum dose to the spinal cord (P = 0.0004) compared to VMAT.
Krhili et al. also found that doses delivered to PTV are similar with both techniques, but the conformity index is improved by 60% with VMAT. Pulmonary protection is improved with the use of VMAT compared to 3DCRT, as the mean lung dose is 12.2 ± 4.5 Gy and 14.1 ± 5.2 Gy, V30 is 14 ± 5% and 20 ± 8%, and V20 is 20 ± 10% and 24 ± 11% (P = 0.002), respectively.
Literature provides enough evidence to support the fact that lung tumors shrink during radiotherapy, with many variations between patients.,,,, Weekly cone-beam CT scans (CBCTs) or mid-treatment repeat planning CT images can be used to predict tumor shrinkage after the initial phase of radiation treatment. Jabbour et al. showed a median target volume reduction of 39.3% (range, 7.3%–69.3%) from day 1 to day 43 CBCTs and also predicted that for every 10% decrease in target volume from day 1 to day 43, the risk of death decreased by 44.3%. Berkovic et al. showed that the average GTV reduction was 42.1% (range, 4.0%–69.3%). The actual GTV reductions were 50.1% for concurrent chemoradiation and 33.7% for sequential chemoradiation patients. Xia et al. also found that mean GTV and PTV decreased by 60.9% and 40.2% when concurrent chemoradiation was planned for lung tumors. In our patients also, tumor shrinkage was seen in all patients in the mid-treatment scan. Mean GTV-P in this study reduced by 31.26% (P = 0.001), mean GTV-N reduced by 50.0% (P = 0.02), and mean PTV reduced by 28.07% (P = 0.001).
Since there was a significant reduction in PTV during lung radiation, and also VMAT plans already found superior to 3DCRT plans in this study, it was imperative to check whether VMAT plans made on shrunken target volumes postinitial phase of treatment (40 Gy) had any significant effect on normal tissues being irradiated or not. Therefore, Phase II plan of 20 Gy in 10 fractions in 2 weeks was made on both pretreatment planning CT scan (plan A) and mid-treatment planning CT scan (plan B). It was interesting to find that, in comparison to plan A, in plan B, for ipsilateral lung, V20 reduced by 3.15% (P = 0.06), though V5 and mean ipsilateral lung dose could not reach a statistically significant reduction. Similarly, for the contralateral lung, V5 reduced by 2.76% (P = 0.001) in plan B, and for combined lung, mean dose reduced by 30% (P = 0.03). Spinal cord dose also showed 30% decrease from 11.36 ± 2.25 Gy in plan A to 7.90 ± 1.12 Gy in plan B. This clearly demonstrates the need and superiority of planning by adaptive radiotherapy in lung tumors treated by concurrent chemoradiation. Berkovic et al. also showed that adaptive radiotherapy offered the most beneficial dosimetric effects when performed around fraction 15. There was a linear relationship between GTV-P volume at a particular fraction and absolute normal tissue volume irradiated. The mean V5, V20, V30, and mean lung dose were found to be increased by 0.8, 3.1, 5.2, and 3.4%, respectively, when virtual lung DVHs were recalculated after rigid fusion of weekly adapted volumes to the initial treatment plan. A similar study by Ding et al. also reported a significant reduction in doses to the lung (V20, 31.60–29.40 cm3, P = 0.00; mean, 17.20–15.90 Gy, p = 0.04), heart (V45, 15.50–15.00 cm3; p = 0.012), and the spinal cord (Dmax, 43.30–40.20 Gy; P = 0.00). Replanning, therefore, undeniably helps in better normal tissue sparing.
The question arises whether all lung cancer patients derive benefit from VMAT plans. On reviewing the individual plans, we could find that patients who had peripherally located tumors could achieve the normal tissue dose constraints by 3DCRT plans also. Majority of the patients in our study had centrally located tumors. Only, three patients had tumor in peripheral location, but due to the presence of mediastinal lymph nodes, the final PTV covered mediastinum also. In these patients, when 3DCRT and VMAT plans were made after excluding lymph nodes from the target volume, we found that the doses received by the spinal cord (Dmax), heart (V20 and mean dose), and contralateral lung (V5 and mean dose) were lesser with 3DCRT plans compared to VMAT plans. Even, the ipsilateral lung and combined lung mean doses were well achieved by 3DCRT plans. Only, the V20 ipsilateral lung dose was higher with 3DCRT plan compared to VMAT plan; still, they were well within constraints.
Since the small patient number was the main limitation of our study, this barred us from conducting a proper analysis based on tumor location (with respect to lung lobes), tumor laterality, and proximity of tumor to normal structures. Thus, the results obtained from this study based on these facts might not be generalized. A randomized study with a large patient number can help deal with these facts and thereby identify patients who will actually benefit from VMAT plans.
| Conclusion|| |
VMAT planning is superior to 3DCRT plans in radiotherapy planning of non-small cell lung tumors, in terms of doses received by normal structures. Mid-treatment planning CT scans and replanning help in more accurate dose delivery to the shrunken target volumes and simultaneously enable better normal tissue sparing.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]